p73 Is Required for pIgR Expression in the Respiratory Epithelium.

Richmond BW, Du RH, Marshall C, Pietenpol J, Polosukhin VV, Blackwell TS
Ann Am Thorac Soc. 2018 15 (Supplement_4): S290

PMID: 30759000 · PMCID: PMC6322007 · DOI:10.1513/AnnalsATS.201806-410MG

RATIONALE - The polymeric immunoglobulin receptor (pIgR) is required for transport of secretory immunoglobulin A across the airway epithelium. Secretory immunoglobulin A helps maintain homeostasis in the airways by preventing bacterial invasion and has been implicated in the pathogenesis of chronic obstructive pulmonary disease.

OBJECTIVES - We investigated whether loss of p73, a transcription factor expressed primarily by multiciliated cells (MCCs), reduces pIgR expression in mice.

METHODS - pIgR expression in p73 null mice (CMV.Cre/Flox-p73) was determined by immunostaining of lung sections and tracheal epithelial cells (TECs) differentiated at the air-liquid interface. pIgR expression in TECs from mice with respiratory epithelium-specific or MCC-specific loss of p73 (SPC.Cre/Flox-p73 and FoxJ.Cre/Flox-p73, respectively) was determined by immunoblotting. Small-airway wall thickness was determined by morphometric analysis in 12-month-old wild-type, pIgR null (pIgR), and CMV.Cre/Flox-p73 mice.

RESULTS - CMV.Cre/Flox-p73 mice had nearly a complete absence of pIgR in vivo and in vitro and spontaneously developed small-airway thickening, which was similar, but more severe, than that observed in pIgR mice. pIgR protein expression was markedly reduced in TECs from SPC.Cre/Flox-p73 and FoxJ1.Cre/Flox-p73 mice, indicating that loss of p73 in the respiratory epithelium or MCCs specifically prevents normal pIgR expression.

CONCLUSIONS - p73 expression by MCCs is required for pIgR expression in mice, suggesting these cells play a key role in maintenance of mucosal immunobarrier function. Future studies should investigate whether p73 is reduced in the airways of patients with chronic obstructive pulmonary disease and the mechanism of pIgR regulation by p73.

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